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The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan.
J Clin Endocrinol Metab 2006; 91(3):1087-92JC

Abstract

CONTEXT

Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. The low incidence of type 1 diabetes in Asian countries, however, makes it difficult to perform large-scale studies in Asia.

OBJECTIVE

To overcome this, we have assembled a multicenter study group in Japan and studied the association of CTLA4 polymorphisms with type 1 diabetes relative to autoimmune thyroid disease (AITD) phenotypes.

SUBJECTS

Subjects included a total of 1837 samples, including 1114 cases (769 with type 1 diabetes and 345 with AITD) and 723 control subjects.

METHODS

The +6230G>A and +49G>A polymorphisms of CTLA4 as well as HLA-DRB1 and -DQB1 were genotyped.

RESULTS

The +6230G>A polymorphism was significantly associated with type 1 diabetes complicated with AITD (odds ratio, 1.54; P = 0.027) and with AITD alone (odds ratio, 1.31; P = 0.045) but not with type 1 diabetes without AITD. The association with type 1 diabetes positive for autoantibodies to both pancreatic islets and thyroid was particularly strong (odds ratio, 1.87; P = 0.001). Type 1 diabetic patients with the disease-associated GG genotype were characterized by a significantly higher frequency of AITD (P = 0.013), of positivity for both AITD and antiislet autoantibody (P = 0.00086), and of high-risk HLA genotypes (P = 0.034).

CONCLUSIONS

Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies.

Authors+Show Affiliations

Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka 565-0871, Japan. ikegami@geriat.med.osaka-u.ac.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16352685

Citation

Ikegami, Hiroshi, et al. "The Association of CTLA4 Polymorphism With Type 1 Diabetes Is Concentrated in Patients Complicated With Autoimmune Thyroid Disease: a Multicenter Collaborative Study in Japan." The Journal of Clinical Endocrinology and Metabolism, vol. 91, no. 3, 2006, pp. 1087-92.
Ikegami H, Awata T, Kawasaki E, et al. The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan. J Clin Endocrinol Metab. 2006;91(3):1087-92.
Ikegami, H., Awata, T., Kawasaki, E., Kobayashi, T., Maruyama, T., Nakanishi, K., ... Ogihara, T. (2006). The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan. The Journal of Clinical Endocrinology and Metabolism, 91(3), pp. 1087-92.
Ikegami H, et al. The Association of CTLA4 Polymorphism With Type 1 Diabetes Is Concentrated in Patients Complicated With Autoimmune Thyroid Disease: a Multicenter Collaborative Study in Japan. J Clin Endocrinol Metab. 2006;91(3):1087-92. PubMed PMID: 16352685.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The association of CTLA4 polymorphism with type 1 diabetes is concentrated in patients complicated with autoimmune thyroid disease: a multicenter collaborative study in Japan. AU - Ikegami,Hiroshi, AU - Awata,Takuya, AU - Kawasaki,Eiji, AU - Kobayashi,Tetsuro, AU - Maruyama,Taro, AU - Nakanishi,Koji, AU - Shimada,Akira, AU - Amemiya,Shin, AU - Kawabata,Yumiko, AU - Kurihara,Susumu, AU - Tanaka,Shoichiro, AU - Kanazawa,Yasuhiko, AU - Mochizuki,Mie, AU - Ogihara,Toshio, Y1 - 2005/12/13/ PY - 2005/12/15/pubmed PY - 2006/6/8/medline PY - 2005/12/15/entrez SP - 1087 EP - 92 JF - The Journal of clinical endocrinology and metabolism JO - J. Clin. Endocrinol. Metab. VL - 91 IS - 3 N2 - CONTEXT: Transracial studies are a powerful tool for genetic association studies of multifactorial diseases, such as type 1 diabetes. The low incidence of type 1 diabetes in Asian countries, however, makes it difficult to perform large-scale studies in Asia. OBJECTIVE: To overcome this, we have assembled a multicenter study group in Japan and studied the association of CTLA4 polymorphisms with type 1 diabetes relative to autoimmune thyroid disease (AITD) phenotypes. SUBJECTS: Subjects included a total of 1837 samples, including 1114 cases (769 with type 1 diabetes and 345 with AITD) and 723 control subjects. METHODS: The +6230G>A and +49G>A polymorphisms of CTLA4 as well as HLA-DRB1 and -DQB1 were genotyped. RESULTS: The +6230G>A polymorphism was significantly associated with type 1 diabetes complicated with AITD (odds ratio, 1.54; P = 0.027) and with AITD alone (odds ratio, 1.31; P = 0.045) but not with type 1 diabetes without AITD. The association with type 1 diabetes positive for autoantibodies to both pancreatic islets and thyroid was particularly strong (odds ratio, 1.87; P = 0.001). Type 1 diabetic patients with the disease-associated GG genotype were characterized by a significantly higher frequency of AITD (P = 0.013), of positivity for both AITD and antiislet autoantibody (P = 0.00086), and of high-risk HLA genotypes (P = 0.034). CONCLUSIONS: Given the high frequency of AITD in patients with type 1 diabetes, these data suggest the possibility that the association of CTLA4 with type 1 diabetes in previous studies may have been secondary to AITD, suggesting the importance of subclassification of type 1 diabetes relative to AITD in genetic studies. SN - 0021-972X UR - https://www.unboundmedicine.com/medline/citation/16352685/The_association_of_CTLA4_polymorphism_with_type_1_diabetes_is_concentrated_in_patients_complicated_with_autoimmune_thyroid_disease:_a_multicenter_collaborative_study_in_Japan_ L2 - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2005-1407 DB - PRIME DP - Unbound Medicine ER -